Hyperpolarized Pyruvate (13C) MR Imaging in Monitoring Patients With Prostate Cancer on Active Surveillance

Phase 2

Recruiting

• Conditions: Prostate Adenocarcinoma; Prostate Cancer
• Interventions: Drug: Hyperpolarized Carbon C 13 Pyruvate; Procedure: Magnetic Resonance Spectroscopic Imaging; Procedure: MRI Ultrasound Fusion Guided Biopsy

• Registration Number: NCT03933670
• Lead Sponsor: University of California, San Francisco

Brief Summary

This phase II trial studies the side how well hyperpolarized carbon C 13 pyruvate (HP C-13 pyruvate) magnetic resonance imaging (MRI) works in monitoring patients with prostate cancer on active surveillance who have not received treatment. Diagnostic procedures, such as MRI, may help visualize HP C-13 pyruvate uptake and breakdown in tumor cells.

Detailed Description

PRIMARY OBJECTIVES:

I. Optimize the imaging sequences that maximize signal-to-noise ratio (SNR) and intra-tumoral conversion of HP 13C pyruvate to lactate (kPL) and HP 13C pyruvate to glutamate (kPG) in regions of tumor versus (vs.) adjacent benign tissue as assessed by multi-parametric MRI (mpMRI) imaging characteristics. (Part 1) II. Determine the association between intra-tumoral kPL and kPG with Gleason grade determined during magnetic resonance (MR)/ultrasound (US)-guided fusion prostate biopsies obtained within 6 months following baseline HP C-13 pyruvate MR exam. (Part 2)

SECONDARY OBJECTIVES:

I. Evaluate the intra-patient variability in intra-tumoral kPL and kPG with repeated dose studies.

II. Determine the association between peak intra-tumoral kPL observed on baseline imaging with serum prostate specific antigen (PSA).

III. Compare and contrast intra-tumoral kPL and kPG with prostate imaging reporting and data system (PI-RADS) version 2 and individual mpMRI parameters including apparent diffusion coefficient (ADC) on diffusion-weighted imaging.

IV. Describe the frequency of up-grading of tumor with MR/US-guided fusion biopsy obtained following baseline HP C-13 MR exam.

V. Further characterize the safety profile of HP C-13 pyruvate injections.

EXPLORATORY OBJECTIVES:

I. Correlate peak intra-tumoral kPL with results of gene expression profiling using DECIPHER assay.

II. Correlate peak intra-tumoral kPL and kPG with DECIPHER GRID tumor ribonucleic acid (RNA) expression of relevant components of the glycolytic pathway including lactate dehydrogenase (LDH), pyruvate dehydrogenase (PDH), aconitate hydratase (aconitase), myelocytomatosis oncogene (MYC), monocarboxylate transporter 4 (MCT4) (lactate transporter).

III. For patients who undergo optional follow-up HP C-13 pyruvate/MRI 6-15 months following baseline scan, determine the mean percent change from baseline in intra-tumoral kPL and kPG and whether the change from baseline is associated change in clinical risk assessment as determined by University of California, San Francisco (UCSF)-Cancer of the Prostate Risk Assessment (CAPRA) risk score.

OUTLINE:

Patients receive hyperpolarized carbon C 13 pyruvate intravenously (IV) over less than one minute, then undergo magnetic resonance spectroscopic imaging (MRSI) after 1-2 minutes. Within 15-60 minutes, patients may receive optional hyperpolarized carbon C 13 pyruvate and undergo MRSI. Patients also undergo MR/US fusion-guided prostate biopsy within 12 weeks following HP C-13 MRSI.

After completion of study, patients will be followed up periodically.

Study Timeline

• Study Start: 2018-07-18
• Study First Submitted: 2019-02-20
• Study First Submitted QC: 2019-04-26
• Study First Posted: 2019-05-01
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-14
• Last Update Posted: 2024-02-16
• Primary Completion: 2025-03-31
• Study Completion: 2025-10-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 60

Inclusion Criteria

• The subject has biopsy-proven adenocarcinoma of the prostate with low to intermediate risk disease by UCSF-CAPRA scoring at study entry.
• For Part 1: Patient planning to enroll or currently on active surveillance; For Part 2: Currently enrolled on active surveillance with planned fusion biopsy within 12 weeks following completion of baseline HP C-13 pyruvate/mpMRI on study.
• The subject is able and willing to comply with study procedures and provide signed and dated informed consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Absolute neutrophil count (ANC) >= 1000 cells/microliter (uL).
• Hemoglobin >= 9.0 gm/deciliter (dL).
• Platelets >= 75,000 cells/uL.
• Estimated creatinine clearance* >= 50 milliliter (mL)/min by the Cockcroft Gault equation.
• Total bilirubin =< 1.5 x upper limit of normal (ULN) or if =< 3 x ULN if known/suspected Gilbert's
• Aspartate aminotransferase (AST) =< 1.5 x ULN.
• Alanine aminotransferase (ALT) =< 1.5 x ULN.

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Exclusion Criteria

• Patients without evidence of any prostate cancer on most recent prostate biopsy performed prior to study entry.
• Current or prior androgen deprivation therapy including luteinizing hormone-releasing hormone (LHRH) analogue or oral anti-androgen therapy. Previous use of a 5-alpha reductase inhibitor is allowed, provided it was discontinued at least 28 days prior to baseline C-13 HP pyruvate MRI
• Prior radiation treatment of the prostate.
• Prostate biopsy performed within 14 days prior to baseline C-13 HP pyruvate MRI.
• Poorly controlled hypertension, with blood pressure at study entry > 160 mm Hg systolic or > 100 mmg Hg diastolic. Treatment with anti-hypertensives and re-screening is permitted.
• Congestive heart failure with New York Heart Association (NYHA) status >= 2.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Diagnostic (HP C-13 MRI)	MRI Ultrasound Fusion Guided Biopsy	Patients receive hyperpolarized carbon C 13 pyruvate IV over less than one minute, then undergo MRSI after 1-2 minutes. Within 15-60 minutes, patients may receive optional hyperpolarized carbon C 13 pyruvate and undergo MRSI. Patients also undergo MR/US fusion-guided prostate biopsy within 12 weeks following HP C-13 MRSI.
Diagnostic (HP C-13 MRI)	Magnetic Resonance Spectroscopic Imaging	Patients receive hyperpolarized carbon C 13 pyruvate IV over less than one minute, then undergo MRSI after 1-2 minutes. Within 15-60 minutes, patients may receive optional hyperpolarized carbon C 13 pyruvate and undergo MRSI. Patients also undergo MR/US fusion-guided prostate biopsy within 12 weeks following HP C-13 MRSI.
Diagnostic (HP C-13 MRI)	Hyperpolarized Carbon C 13 Pyruvate	Patients receive hyperpolarized carbon C 13 pyruvate IV over less than one minute, then undergo MRSI after 1-2 minutes. Within 15-60 minutes, patients may receive optional hyperpolarized carbon C 13 pyruvate and undergo MRSI. Patients also undergo MR/US fusion-guided prostate biopsy within 12 weeks following HP C-13 MRSI.

Primary Outcome Measures

Name	Time	Method
Intra-tumoral C-pyruvate to glutamate (kPG)	At Baseline	Assessed by multi-parametric magnetic resonance imaging (mpMRI) characteristics
Association between intra-tumoral C-pyruvate to lactate (kPL) with Gleason grade	Within 12 weeks following baseline HP C-13 pyruvate MR exam	kPL will be compared with the pathologic Gleason grade determined using tissue from an MR/US-guided fusion prostate biopsy. Measured kPL will be compared by pathologic Gleason grade using an ANOVA model. If there is an overall difference, the Newman-Keuls post hoc test will be used to determine which tissue pairs differ.
Association between intra-tumoral C-pyruvate to glutamate (kPG) with Gleason grade	Within 12 weeks following baseline HP C-13 pyruvate MR exam	kPG will be compared with the pathologic Gleason grade determined using tissue from an MR/US-guided fusion prostate biopsy. Measured kPG will be compared by pathologic Gleason grade using an ANOVA model. If there is an overall difference, the Newman-Keuls post hoc test will be used to determine which tissue pairs differ.
Signal-to-noise ratio (SNR) of hyperpolarized lactate	At Baseline	Assessed by multi-parametric magnetic resonance imaging (mpMRI) characteristics.
Intra-tumoral C-pyruvate to lactate (kPL)	At Baseline	Assessed by multi-parametric magnetic resonance imaging (mpMRI) characteristics

Secondary Outcome Measures

Name	Time	Method
Intra-patient variability in kPL	Up to 15 months	Intra-patient variability in the kPL will be summarized by the intraclass correlation and presented with a 90% confidence interval.
Intra-patient variability in kPG	Up to 15 months	Intra-patient variability in the kPG will be summarized by the intraclass correlation and presented with a 90% confidence interval.
Association between peak intra-tumoral kPL observed on baseline imaging with serum PSA	At Baseline	Determine the association between peak intra-tumoral kPL observed on baseline imaging with serum PSA. The study cohort will be dichotomized by mean intra-tumoral kPL above and below the median and the mean serum PSA will be compared between the two dichotomized subgroups using Mann-Whitney test.
Describe frequency of up-grading of tumor	Within 12 weeks following baseline HP C-13 pyruvate MR exam	Describe the frequency of up-grading of tumor with MR/US-guided fusion biopsy obtained following baseline HP C-13 MR exam
Contrast between kPL and kPG in regions of tumor	Up to 15 months	The kPL and kPG will be contrasted in regions of tumor. Determined with prostate imaging reporting and data system (PI-RADS) version 2 classification score (1 through 5)
Comparison of kPL and kPG with apparent diffusion coefficient in region of tumor	Up to 15 months	The kPL and kPG will be compared with apparent diffusion coefficient in region of tumor. Determined by comparison to peak intra-tumoral apparent diffusion coefficient (ADC) value
Incidence of adverse events graded	Up to 15 months	According to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.

Trial Locations

Locations (1)

University of California, San Francisco; 🇺🇸 San Francisco, California, United States